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Quantum Dots for interaoperative Margin Determination during Breast Cancer Surgury

(W.H. Shih, A. Brooks, W.Y. Shih, and V. Swami)

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Abstract: Margin determination is critical for breast conserving surgery. Studies have shown that the local recurrence rate is higher for positive or close margin (16%) than that for negative margin (6%). Incomplete tumor removal, when detected by post-operative analysis, requires re-excision or second surgery, which doubles the cost and adds significant discomfort to the patient. Furthermore, morbidity and recurrence rates are much higher in patients who undergo re-excision. Current breast cancer re-excision rate is estimated to range from 15% to as higher as 60%. Intraoperative tumor margin determination would enable complete tumor removal during the first surgery while the patient is still on the operating table. Current procedures for margin assessment include touch preparation cytology (TPC) and frozen section analysis (FSA), which are time-consuming and unreliable. Our quantum dot-based technology is a molecular fluorescence imaging tool that can specifically identify cancerous cells for intraoperative lumpectomy margin assessment. The approach uses the aqueous quantum dots (AQDs) developed in our lab as contrasting agent coupled with antibodies for cancer cells detection. The procedure involves spraying excised tissue with AQDs conjugated with antibody specific to cancer-associated antigen followed by rinsing and examining the excised tissue with an imaging system. The intensity of the photoluminescence (PL) will indicate if cancer cells are on or in close proximity to the excised tissue surface. The information will help surgeons make timely decision whether to have re-excision right in the surgery room. The final product will be an intraoperative test kit that consists of antibody conjugated AQDs and an imaging system to image the excised samples. Preliminary results indicate the cancer-associated antigen-conjugated AQDs exhibit better than 96% sensitivity and better than 90% specificity in identifying cancer cells in tissues.